KalVista's Sebetralstat Marketing Authorization Application Validated by EMA for Hereditary Angioedema

KalVista Pharmaceuticals, Inc. has announced that the European Medicines Agency (EMA) has validated their Marketing Authorization Application (MAA) for sebetralstat, an innovative oral plasma kallikrein inhibitor designed for the on-demand treatment of hereditary angioedema (HAE). This validation marks a significant milestone, advancing the process towards sebetralstat potentially becoming the first oral, on-demand treatment for HAE in Europe. The application will undergo evaluation by the EMA’s Committee for Medicinal Products for Human Use (CHMP) under the centralized licensing procedure, encompassing all 27 EU Member States as well as the EEA countries Norway, Iceland, and Liechtenstein.

Ben Palleiko, the CEO of KalVista, expressed enthusiasm about this development, highlighting that if approved, sebetralstat could address unmet needs within the HAE community, potentially becoming a foundational treatment for the condition.

The MAA submission was bolstered by results from the KONFIDENT phase 3 clinical trial and the ongoing KONFIDENT-S open label extension trial. Sebetralstat showed promising outcomes, meeting the primary endpoint of its phase 3 trial with both 300 mg and 600 mg formulations providing quicker symptom relief compared to placebo. The medication was well-tolerated, showing a safety profile akin to placebo. In the KONFIDENT-S trial, data indicated that patients were able to treat attacks earlier, with a median time from attack onset to treatment of nine minutes and a median time to beginning of symptom relief for laryngeal attacks of 1.3 hours.

The detailed results from the KONFIDENT trial were published in The New England Journal of Medicine and were presented at the European Academy of Allergy and Clinical Immunology Congress 2024. Additionally, KalVista submitted a New Drug Application (NDA) for sebetralstat to the U.S. Food & Drug Administration (FDA) in June 2024. Future plans include presenting EU-specific data from the KONFIDENT trial and additional data from KONFIDENT-S at the 7th Bradykinin Symposium in Berlin, Germany, in September 2024.

KalVista has also launched the KONFIDENT-KID clinical trial, which aims to assess the safety and efficacy of sebetralstat in a pediatric population aged 2-11 years. This trial will provide critical data over a one-year period and features a pediatric oral disintegrating tablet (ODT) formulation of sebetralstat.

The KONFIDENT phase 3 trial was an extensive, randomized, double-blind, 3-way crossover study involving 136 HAE patients from 66 clinical sites across 20 countries, making it the largest clinical trial ever conducted for HAE. Participants were allowed to treat up to three attacks during the study, which included both type 1 and type 2 HAE patients. The trial included patients who had experienced at least two documented HAE attacks within 90 days prior to randomization, including those on long-term prophylaxis.

The KONFIDENT-S trial, an open label extension, continues to evaluate the long-term safety and efficacy of sebetralstat in adult and pediatric patients aged 12 and older. KalVista plans to transition participants in this trial to an ODT formulation in late 2024, aiming for a supplemental NDA filing in 2026 for this new formulation, potentially providing an alternative oral treatment option for HAE patients.

The KONFIDENT-KID trial is designed to enroll approximately 24 children across seven countries in North America, Europe, and Asia. This trial will gather safety, pharmacokinetic, and efficacy data over a one-year period, with the hope that sebetralstat will become the first oral on-demand therapy for this young age group.

Sebetralstat, discovered and developed by KalVista's scientific team, is an investigational oral plasma kallikrein inhibitor intended for the on-demand treatment of HAE. It has received Fast Track and Orphan Drug Designations from the U.S. FDA, along with similar designations and an approved Pediatric Investigational Plan from the EMA.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by painful and debilitating attacks of tissue swelling in various parts of the body, which can be life-threatening. Current treatments for HAE require either intravenous or subcutaneous administration, underscoring the potential impact of an effective oral treatment like sebetralstat.

KalVista Pharmaceuticals is focused on developing and delivering oral medications for diseases with significant unmet needs. Following positive phase 3 data from the KONFIDENT trial, KalVista has proceeded with regulatory submissions in the U.S. and Europe and plans to seek approval in the UK, Japan, and other regions in the near future.